A diastereoselective, catalytic Co<sub>2</sub>(CO)<sub>8</sub>-mediated Pauson−Khand reaction (PKR) of siloxy-tethered 1,7-enynes for the synthesis of cyclopentaoxasilinones has been developed. Oxidation of the resulting cyclopentaoxasilinones delivers stereoenriched β-alkylated cyclopentenones, which are inaccessible by intermolecular PKRs. Since its initial discovery in 1973, the intra- and intermolecular PKRs have been exemplified as a convergent, atom-economical, and fundamental reaction for the [2+2+1] synthesis of cyclopentenones. However, the intermolecular PKR has generally been limited to strained or symmetrical alkenes due to the difficulty controlling the alkene regio- and stereoselectivity. Therefore, a general stereoselective PKR strategy to access highly functionalized monocyclic cyclopentenones remains an unsolved challenge. Herein, we describe the use of 1,7- enynes bearing a removable silicon tether, that upon oxidation of the Si-C bond, gives rise to highly functionalized and stereoenriched monocyclic cyclopentenones bearing functionalizable handles, allowing a rapid introduction of stereochemical complexity and structural diversity. The utilization of secondary propargylic alcohols bearing a terminal olefin has led to unprecedented diastereoselectivity of which we are currently investigating its origins via a computational collaboration with the Houk Group at UCLA. We are also developing a catalytic variation of the above method that invokes the use of ex-situ generated carbon monoxide from cheap and benign commodity chemicals to mitigate the hazards of working with this gas. The utilization of the above method in the total synthesis of a family of iridoid natural products is currently underway in our lab.

Access to highly functionalized cyclopentenones via catalytic diastereoselective Pauson-Khand reaction of Si-O tethered 1,7-enynes

ACS Spring Meeting 2021

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